In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the importantcaution:It is uncertain whether Met-1 or Met-8 is the initiator.,disease:Defects in MPL are a cause of congenital amegakaryocytic thrombocytopenia (CAMT) [MIM:604498]. CAMT is a disease characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies.,domain:The box 1 motif is required for JAK interaction and/or activation.,domain:The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.,function:Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.,similarity:Belongs to the type I cytokine receptor family. Type 1 subfamily.,similarity:Contains 2 fibronectin type-III domains.,subunit:Interacts with ATXN2L.,tissue specificity:Expressed at a low level in a large number of cells of hematopoietic origin. Isoform 1 and isoform 2 are always found to be coexpressed.,
